Reversible phosphorylation of hydroxymethylglutaryl CoA (HMCoA) was shown for the first time in nonhepatic human cells in vitro. Phosphorylated and dephosphorylated (active) forms of the enzyme wee assayed in human skin fibroblasts grown in culture. Short-term (30-60 min.) incubation in medium containing lipoproteins of fibroblasts, that had previously been maintained in lipid-free medium, caused inactivation of the enzyme, which was reversed by the action of phosphatase. Longer incubation with lipoproteins caused irreversible inhibition of the enzyme. Mevalonolactone exerted an influence on HMGCoA reductase similar to that of serum lipoproteins.